Hao Qian

Three-dimensional conformal radiotherapy for locoregionally recurrent lung carcinoma after external beam irradiation: a prospective phase I-II clinical trial.

OBJECTIVES To observe in a clinical trial the feasibility, tolerance, and efficacy of reirradiation by three-dimensional conformal radiotherapy (3D-CRT) for locoregionally recurrent lung carcinoma after external beam radiotherapy (EBRT). MATERIALS AND METHODS Between June 1999 and March 2001, 23 lung carcinoma patients with locoregional recurrence after EBRT were enrolled in this study. Of the 23 patients, 21 were men and 2 were women (median age 68 years, range 43-79). At the first course of RT, 9 patients had squamous cell carcinoma, 7 adenocarcinoma, and 7 small cell carcinoma. The interval between the first course of RT and recurrence varied from 6 to 42 months (median 13). The median dose of the first course of RT was 66 Gy (range 30-78). Reirradiation was carried out using 3D-CRT and only covered the radiographic lesions. The median dose of reirradiation was 51 Gy (range 46-60), which was delivered by a conventionally fractionated schedule (i.e., 1.8-2.0 Gy/fraction, 5 fractions/wk). The toxicity was assessed according to the Radiation Therapy Oncology Group criteria. RESULTS The median follow-up time was 15 months (range 2-37). Acute radiation esophagitis occurred in 9% of patients (Grade 1-2). Acute radiation pneumonitis developed in 22% of patients (Grade 1-2). No cases of acute Grade 3 or greater toxicity had been recorded at last follow-up. Pulmonary fibrosis was observed in 26% of patients (Grade 2-3); no other severe late complications have been observed. The 1- and 2-year survival rate was 59% and 21%, respectively. The locoregional progression-free rate at 1 and 2 years was 51% and 42%, respectively. CONCLUSIONS Reirradiation using 3D-CRT was tolerated by this group of recurrent lung carcinoma patients without severe complications. The 2-year outcome was encouraging. Reirradiation with 3D-CRT can be considered an option for the management of locoregionally recurrent lung carcinoma.

The impact of overall treatment time on outcomes in radiation therapy for non-small cell lung cancer

PURPOSE A retrospective study was carried out to evaluate the impact of overall treatment time (OTT) on the results of radiation therapy for non-small cell lung cancer (NSCLC). MATERIALS AND METHODS From Jan. 1990 to Dec. 1996, 256 patients with stages I-IIIb NSCLC entered this analysis. All patients received definitive radiotherapy. Biologically effective dose (BED) was used to standardize the irradiation effects. The correlation between OTT and local progression-free survival was analyzed by linear-regression and Cox proportional hazard models. The prognostic variables for survival and distant metastasis were also briefly studied. RESULTS OTT had been shortened in 64 patients because of an accelerated hyperfractioned irradiation, while OTT was prolonged i n 114 patients due to interruptions of irradiation courses. The main ca uses of interruption were machine breakdown or delayed preparations of c errobend block for boost fields (55%), holidays (11%) and treatment toxi city and side effects (34%). Patients tre ated with prolonged OTT (> 45 days) had significant poorer local progression-free survival than whom with OTT of </=45 days, 1, 3 and 5 year actuarial local progression-free survivals being 49, 17 and 15% for the former, and 74, 35 and 25% for the latter, respectively (P<0.001). BED-T that contained the factor of OTT correlated directly to local controls, which implied that BED-T represented radiobiological effects accurately, in other words, OTT had played a role in determining the radiobiological effects. Linear-regression on 103 cases treated with BED of 80-85 Gy(10) showed that 3 year local progression-free survival decreased by 9% per week with prolongation of OTT, or vice versa it increased by 9% per week with shortening OTT in an OTT range of 30-76 days. Cox multivariate analyses confirmed that OTT was an independent prognostic factor for local controls. CONCLUSION OTT may have played an important role in determining local controls in radiotherapy for NSCLC. One should always keep in mind to make the OTT as short as possible, provided the patients can tolerate it, and to reduce irradiation interruptions for whatever reasons to a minimum.

Three-dimensional conformal radiation therapy for non-small-cell lung cancer: a phase I/II dose escalation clinical trial.

PURPOSE A prospective Phase I/II dose escalation study was conducted to determine the maximum tolerated dose (MTD) in three-dimensional conformal radiation therapy (3D-CRT) for non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS MTD would be reached via a dose escalation study. After 42 Gy/21 fractions, 4.2 weeks by conventional fractionated irradiation through anteroposterior/posteroanterior fields, the 3D-CRT technique was used as boost. The planned total dose escalation depended on lung volume irradiated. According to the percentage of lung volume receiving >20 Gy, the patients were divided into three subgroups (i.e., <25%, 25%-37%, and >37%). The scheduled dose escalation began with 69 Gy and continued to 78 Gy. The boost doses were delivered at 3 Gy per fraction, once per day, five fractions per week. Each dose level includes 5 patients. Besides radiotherapy, all patients received neoadjuvant and adjuvant chemotherapy with MVP regimen (Mitomycin, Vindesine, cis-platium). The criterion for stopping further dose escalation was > or =20% of patients with > or =RTOG Grade 3 radiation pneumonitis. RESULTS Between June 1999 and February 2001, 50 patients had been enrolled in this study, including 4 with Stage II disease, 31 with Stage IIIa disease, and 15 with Stage IIIb disease. The dose escalation plan has been completed. All subgroups reached the highest predetermined dose levels (i.e., 78 Gy for the <25% subgroup, 78 Gy for the 25-37% subgroup, and 75 Gy for the >37% subgroup). Although none of the subgroups developed more than 20% of >/=Grade 3 acute pneumonitis, dose escalation was terminated because long-term follow-up was needed to observe late complications. Median follow-up time (MFT) for the entire group was 18 months (6-37 months). The most common acute complication was esophagitis in 56% of patients with RTOG Grade 1-2, and in 4% with Grade 3. Acute radiation pneumonitis developed in 36% of patients with RTOG Grade 1-2. Only 1 patient had Grade 3 pneumonitis, which was in the 25-37% subgroup at 75 Gy. The hematopoietic toxicity appeared in 58% of patients with Grade 1-2, and 8% with Grade 3. As to late complications, only 30% of patients developed pulmonary fibrosis of RTOG Grade 1-2. The median survival time for the entire group was 18 months. Two-year overall survival, locoregional progression-free rate, and distant metastasis rate were 44%, 40%, and 41%, respectively. CONCLUSIONS Although MFT was 18 months, it had not yet been declared because a longer follow-up was needed to observe the late complications. The 2-year overall survival of 44% was very encouraging and implied that 3D-CRT combined with chemotherapy would improve the outcome for locally advanced NSCLC.

Prognostic predictors and long-term outcome of postoperative irradiation in thymoma: a study of 241 patients.

ABSTRACT The purpose of this study was to identify the prognostic predictors treated with postoperative irradiation in patients with thymoma. Two hundred forty-one patients with histologically confirmed thymoma were collected and retrospectively reviewed in this study. Fifty-four patients had stage I disease; 57, stage II; 120, stage III; 10, stage IV. One hundred sixty patients underwent total thymectomy; 63, partial resection; 18, debulking or biopsy. Patients were irradiated after surgery with median dose of 50 Gy by conventional fractionation. The overall survival rates at 5 and 10 years were 83.1% and 72.6%, respectively. The 10-year overall survival was 87% for stage I, 78.7% for stage II, 57.4% for stage III, and 24.3% for stage IV. The conclusions were drawn from this analysis. For stage I, the role of postoperative irradiation needed further investigation. For stage II–III, surgery and postoperative irradiation should be part of standard care. The favorable prognostic predictors were female, early stage, and surgical extirpation.

Three-dimensional conformal radiation therapy for squamous cell carcinoma of the esophagus: A prospective phase I/II study

PURPOSE A prospective phase I-II study was conducted to determine the tolerance and local control rate of three-dimensional conformal radiotherapy (3-DCRT) for esophageal squamous cell carcinoma (SCC). METHODS AND MATERIALS Thirty patients underwent 3-DCRT for thoracic esophageal SCC. PTV1 composed of a 1.2-1.5 cm margin lateral around GTV and 3.0 cm margin superior/inferior of GTV. PTV2 encompassed GTV with a margin of 0.5-0.7 cm. The dose for PTV1 was 50 Gy in 2 Gy daily fractions; PTV2 received a boost of 16 Gy in 2 Gy daily fractions to a total dose of 66 Gy. RESULTS Median follow-up time was 18 months. The most common acute toxicity was esophagitis in 63% of patients with RTOG grades 1-2, and in 3% with grade 3. RTOG grades 1-2 radiation pneumonitis developed in 27% of patients. One patient developed pulmonary fibrosis RTOG grade 2 and another patient experienced grade 3 pulmonary fibrosis. Two patients developed mild esophageal stricture requiring dilatation. Two-year overall survival, local disease progression-free rate, and distant metastasis-free rate were 69%, 36% and 56%, respectively. CONCLUSIONS Although 3-DCRT to 66 Gy for esophageal SCC was well tolerated, the local control was disappointing. The result supports the use of chemoradiation as the standard care for esophageal SCC.

[Phase I clinical trial of dose escalation on three dimensional conformal radiation therapy for non-small cell lung cancer].

BACKGROUND To establish the technique of 3-dimensional conformal radiation therapy (3DCRT) for non-small cell lung cancer (NSCLC) in stage II-IIIB,and to assess its acute side-effects and to obtain the maximum tolerance dose (MTD). METHODS From June,1999 to June,2000,38 cases of NSCLC in stage II-IIIB were enrolled in this study.MTD was identified by dose escalation study.After 42Gy/21Fx/4.2wks by conventional fractionated irradiation through AP/PA fields,which covered the primary tumor and lymph nodes,the technique of 3DCRT was used as boost.The boost fields encompassed the clinical lesions showed on chest CT.The planning of total dose escalation depended on the percentage,i.e.,<25%,25%-37%,and >37% of normal lung volume irradiated to over 20Gy.The scheduled dose escalation ranged from 69 to 81Gy.The criteria for stopping dose escalation was grade III or more worse radiation pneumonitis (RTOG).The boost doses were delivered with 3Gy/fraction,once a day,5 fractions a week. RESULTS Thirty-three cases had completed their treatments and could be evaluated by now.Acute radiation pneumonitis occurred in 26% of patients with grade I-II and 3% with grade III,and acute radiation esophagitis in 61% with grade I-II and 9% with grade III,and the hematopoietic toxicity in 58% with grade I-II and 9% with grade III.The current doses implemented were 78,78,and 75Gy respectively for patients with <25%,25%-37%,and >37% of normal lung volume irradiated.The overall immediate response rate of tumors was 88%(29/33). CONCLUSIONS Dose escalation in a volume-dependent organ as the lungs is acceptable and applicable.The immediate response is encouraging.MTD is to be determined.The long-term follow-up is needed to observe late complications and treatment efficacy.